HDL are heterogeneous and the major lipoprotein particles include LpA- I,and LpA-I:A-II. Current data based on epidemiological, cell culture, as well as transgenic animal studies are consistent with LpA-I being the antiatherogenic particle within HDL. In our previous studies we have established that LpA-I is catabolized at a faster rate than LpA-I:A-II. LpA-I:A-II is fromed by the addition of apoA-II to LpA-I particles. Three subclasses of LpA-I are present in human plasma. These three subclasses designated Large, Medium, and Small have different lipid and apolipoprotein composition as well as concentrations of CETP and LCAT activities indicating the important heterogeneity of the LpA-I particles. Women have a higher plasma concentration than men of only the Large LpA-I particle with similar concentration of the Middle and Small LpA-I particles. The metabolism of the three LpA-I particles was investigated in normal control subjects. The catabolism of the Small LpA-I was the fastest of the three LpA-I particles clearly establishing that the catabolism of LpA-I is critically dependent on the size of the LpA-I particle. To gain insight into the metabolism of LpA-I and LpA-I:A-II kinetic studies were performed in fifty normolipidemic subjects and the associations with lipids and apolipoprotein levels determined. Triglyceride levels inversely correlated with only LpA-I. ApoA-I levels were most strongly correlated with the catabolic rate. ApoA-II levels were only correlated with synthesis rate. Plasma LpA-I levels are correlated with the catabolism of both apoA-I and apoA-II while LpA-I:A- II levels were correlated with the synthesis rates of apoA-I and apoA-II. Based on multiple regression analysis the production rate of apoA-II is the only independent kinetic parameter determining the plasma LpA-I levels. Further studies are underway to investigate additional parameters that modulate LpA-I and LpA-I:A-II metabolism. These studies included subjects of age 19 to 47. 52% of the study subjects were women, seven were Asian, and three were Indian.